Daily Anesthesiology Research Analysis
Three perioperative studies stand out today: a multicenter randomized trial shows single-shot intercostal nerve block is noninferior to thoracic epidural for pain after thoracoscopic lung resection while enhancing recovery; a dual-center randomized trial finds norepinephrine infusion (dose-equivalent) is as safe as phenylephrine for preventing spinal-induced hypotension in cesarean delivery with less bradycardia; and a validated multicenter machine-learning model accurately predicts death within
Summary
Three perioperative studies stand out today: a multicenter randomized trial shows single-shot intercostal nerve block is noninferior to thoracic epidural for pain after thoracoscopic lung resection while enhancing recovery; a dual-center randomized trial finds norepinephrine infusion (dose-equivalent) is as safe as phenylephrine for preventing spinal-induced hypotension in cesarean delivery with less bradycardia; and a validated multicenter machine-learning model accurately predicts death within 1 hour after terminal extubation in PICUs, informing DCDD planning and family counseling.
Research Themes
- Thoracic perioperative analgesia and enhanced recovery
- Vasopressor choice in obstetric anesthesia
- Predictive analytics for end-of-life and organ donation in critical care
Selected Articles
1. Intercostal or Paravertebral Block vs Thoracic Epidural in Lung Surgery: A Randomized Noninferiority Trial.
In a multicenter randomized trial of thoracoscopic lung resections, single-shot intercostal nerve block achieved noninferior pain control to thoracic epidural over POD0–2 while reducing opioid use and improving mobilization; length of stay was shorter with ICNB. Continuous paravertebral block was inferior to epidural for pain but also reduced opioids and enhanced mobility.
Impact: This is high-quality randomized evidence that a simpler, less invasive block can replace epidural analgesia for VATS lobectomy/segmentectomy without sacrificing pain control and with better recovery metrics.
Clinical Implications: For thoracoscopic anatomical lung resections, ICNB can be adopted as a first-line regional strategy in ERAS pathways when epidural is undesirable, balancing analgesia with fewer side effects, easier mobilization, and shorter hospitalization.
Key Findings
- ICNB was noninferior to TEA for the proportion of pain scores ≥4 on POD0–2 (upper 1-sided 98.65% CI 16.1%).
- PVB was inferior to TEA for pain (upper limit > noninferiority margin).
- ICNB and PVB reduced opioid consumption and enhanced mobilization compared with TEA.
- ICNB was associated with shorter hospital stay; QoR-15 scores were similar among groups.
Methodological Strengths
- Multicenter randomized design with both ITT and per-protocol analyses
- Predefined noninferiority margin for pain and superiority assessment for QoR; clinically relevant secondary endpoints
Limitations
- Open-label design may introduce performance bias
- Regional practice patterns and adjuncts could vary across centers; generalizability beyond VATS anatomical resections uncertain
Future Directions: Head-to-head trials of ICNB protocols (e.g., multi-level, liposomal local anesthetics), cost-effectiveness analyses, and pragmatic implementation studies across diverse thoracic procedures.
IMPORTANCE: Effective pain control after thoracic surgery is crucial for enhanced recovery. While thoracic epidural analgesia (TEA) traditionally ensures optimal analgesia, its adverse effects conflict with the principles of enhanced recovery after thoracic surgery. High-quality randomized data regarding less invasive alternative locoregional techniques are lacking. OBJECTIVE: To evaluate the efficacy of continuous paravertebral block (PVB) and a single-shot intercostal nerve block (ICNB) as alternatives to TEA. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial compared PVB and ICNB vs TEA (1:1:1) in patients undergoing thoracoscopic anatomical lung resection at 11 hospitals in the Netherlands and Belgium, enrolled from March 5, 2021, to September 5, 2023. The study used a noninferiority design for pain and a superiority design for quality of recovery (QoR). INTERVENTIONS: Continuous PVB and single-shot ICNB. MAIN OUTCOMES AND MEASURES: Primary outcomes were pain, defined as mean proportion of pain scores 4 or greater during postoperative days (POD) 0 through 2 (noninferiority margin for the upper limit [UL] 1-sided 98.65% CI, 17.5%), and QoR, assessed with the QoR-15 questionnaire at POD 1 and 2. Secondary measures included opioid consumption, mobilization, complications, and hospitalization. RESULTS: A total of 450 patients were randomized, with 389 included in the intention-to-treat (ITT) analysis (mean [SD] age, 66 [9] years; 208 female patients [54%] and 181 male [46%]). Of these 389 patients, 131 received TEA, 134 received PVB, and 124 received ICNB. The mean proportions of pain scores 4 or greater were 20.7% (95% CI, 16.5%-24.9%) for TEA, 35.5% (95% CI, 30.1%-40.8%) for PVB, and 29.5% (95% CI, 24.6%-34.4%) for ICNB. While PVB was inferior to TEA regarding pain (ITT: UL, 22.4%; analysis per-protocol [PP]: UL, 23.1%), ICNB was noninferior to TEA (ITT: UL, 16.1%; PP: UL, 17.0%). The mean (SD) QoR-15 scores were similar across groups: 104.96 (20.47) for TEA, 106.06 (17.94; P = .641) for PVB (P = .64 for that comparison), and 106.85 (21.11) for ICNB (P = .47 for that comparison). Both ICNB and PVB significantly reduced opioid consumption and enhanced mobility compared with TEA, with no significant differences in complications. Hospitalization was shorter in the ICNB group. CONCLUSIONS AND RELEVANCE: After thoracoscopic anatomical lung resection, only ICNB provides noninferior pain relief compared with TEA. ICNB emerges as an alternative to TEA, although risks and benefits should be weighed for optimal personalized pain control. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05491239.
2. Death One Hour After Terminal Extubation in Children: Validation of a Machine Learning Model to Predict Cardiac Death After Withdrawal of Life-Sustaining Treatment in a Multicenter Cohort, 2009-2021.
Using multicenter retrospective data from 10 PICUs, a parsimonious extra-trees model with 21 variables predicted death within one hour after terminal extubation with AUC 0.84 and PPV 88% at 90% sensitivity, and was temporally and externally validated. Performance held among potential DCDD donors, supporting clinical logistics and counseling.
Impact: This study provides validated predictive tooling for a time-critical endpoint with direct implications for family counseling and DCDD feasibility, an area lacking robust, generalizable models.
Clinical Implications: PICUs can use such models to anticipate the likelihood of death within 1 hour post-extubation, better counsel families, align multidisciplinary teams, and streamline DCDD processes when desired.
Key Findings
- Extra-trees model (21 features) achieved AUC 0.84 (95% CI 0.81–0.87) on external temporal validation.
- At 90% sensitivity, PPV was 88%, NPV 70%, with number needed to alert 1.14.
- Among potential DCDD donors, PPV 86% and NPV 74% at the same sensitivity.
- Model trained on 8 sites (2009–2018) and validated on all 10 sites (2019–2021), supporting generalizability.
Methodological Strengths
- Multisite dataset with temporal and external validation enhancing generalizability
- Parsimonious feature set facilitating interpretability and clinical implementation with strong discrimination
Limitations
- Retrospective observational design susceptible to unmeasured confounding and documentation biases
- Model calibration and fairness across subgroups were not extensively reported; implementation and ethical frameworks are needed
Future Directions: Prospective validation with real-time integration, calibration and fairness audits, and decision-support trials to assess effects on counseling, DCDD logistics, and resource utilization.
OBJECTIVES: In the PICU, predicting death within 1 hour after terminal extubation (TE) is valuable in augmenting family counseling and in identifying suitable candidates for organ donation after circulatory determination of death (DCDD). The objective of this study was to train and validate a machine learning model to predict death within 1 hour after TE. DESIGN: The Death One Hour After Terminal Extubation (DONATE) database was generated using multicenter retrospective data from 2009 to 2021. Data covering demographics, clinical features, vital signs, laboratory values, ventilator settings, medications, and procedures were collected. Machine learning models were trained to predict whether a pediatric patient would die within 1 hour after TE and evaluated on a holdout set. SETTING: Ten U.S. PICUs. PATIENTS: Children and adolescents, 0-21 years old, who died after TE ( n = 957). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The final model was a parsimonious extra-trees model with 21 input features. It was trained on the 2009-2018 data from eight sites ( n = 634) and evaluated on a holdout set comprised of the 2019-2021 data of all ten sites ( n = 323), representing temporal and external validation. The area under the receiver operating characteristic curve and 95% CI was 0.84 (95% CI, 0.81-0.87). At a sensitivity of 90%, the positive predictive value (PPV) was 88%, the negative predictive value (NPV) was 70%, and the number needed to alert (NNA) was 1.14. Among potential organ donors, at the same sensitivity level, the PPV was 86%, the NPV was 74%, and the NNA was 1.17. CONCLUSIONS: Our model, trained and validated on multisite data, predicted whether a child will die within 1 hour of TE with high discrimination and a low false alarm rate. This finding has important applications to end-of-life counseling and institutional resource utilization when families wish to attempt DCDD.
3. Effects of Prophylactic Infusion of Equivalent Doses of Norepinephrine and Phenylephrine in Preventing Spinal Anesthesia-Induced Hypotension During Cesarean Delivery on Fetal and Maternal Outcomes: A Dual-Center, Non-Inferiority Controlled Trial.
In a dual-center randomized noninferiority trial with dose-equivalent infusions, norepinephrine (0.10 μg/kg/min) was noninferior to phenylephrine (0.60 μg/kg/min) for neonatal UA pH and had similar hypotension rates but significantly less bradycardia. Neonatal outcomes were comparable between groups.
Impact: This trial addresses dose-equivalence rigorously and supports norepinephrine as a bradycardia-sparing first-line vasopressor for spinal hypotension in cesarean delivery.
Clinical Implications: Norepinephrine infusion at dose-equivalent rates can be used to prevent spinal-induced hypotension in cesarean delivery with reduced bradycardia risk compared with phenylephrine, without compromising neonatal acid-base status.
Key Findings
- Neonatal UA pH with norepinephrine was noninferior to phenylephrine (mean difference 0.003; 95% CI -0.016 to 0.022; P=0.009).
- Maternal hypotension incidence was similar (8.3% NE vs 10.6% PE; P=0.701).
- Bradycardia was significantly less frequent with norepinephrine (2.1% vs 12.8%; P=0.046).
- Neonatal outcomes beyond UA pH were comparable between groups.
Methodological Strengths
- Randomized allocation with dose-equivalent comparison across two centers
- Clinically meaningful primary endpoint (neonatal UA pH) with predefined noninferiority framework
Limitations
- Modest sample size limits power for rare adverse events and subgroup analyses
- Short-term outcomes; no long-term maternal or neonatal follow-up
Future Directions: Larger multicenter trials with long-term follow-up and evaluation of closed-loop vasopressor titration comparing norepinephrine vs phenylephrine across diverse obstetric populations.
BACKGROUND: Numerous studies have compared the effects of norepinephrine and phenylephrine on maternal and neonatal outcomes during cesarean delivery. However, the infusion rates are often based on clinical experience, resulting in non-equivalent doses. We aimed to compare the effects of norepinephrine and phenylephrine at equivalent doses on fetal and maternal outcomes, and assess their efficacy at the 90% effective dose (ED METHODS: A total of 100 parturients scheduled for cesarean delivery were randomly allocated to receive either 0.10 μg/kg/min norepinephrine (Group NE) or 0.60 μg/kg/min phenylephrine (Group PE) to prevent spinal anesthesia-induced hypotension. The primary endpoint was neonatal umbilical arterial (UA) pH and the incidence of maternal hypotension, while secondary endpoints included hemodynamic changes within the first 15 minutes, maternal adverse events, and additional neonatal measures. RESULTS: Of the 95 subjects who completed the study, the UA pH in Group NE (7.296 ± 0.041) was found to be non-inferior to Group PE (7.292 ± 0.040), with a mean difference of 0.003 [95% confidence interval (CI): -0.016 to 0.022; P = 0.009]. The incidences of hypotension (NE: 8.3% vs PE: 10.6%, P = 0.701), hypertension, nausea, and vomiting were comparable between groups. However, bradycardia incidence was significantly reduced in Group NE compared to Group PE (2.1% vs 12.8%, P = 0.046). The two groups showed no significant difference in systolic blood pressure (SBP) at most time points within the first 15 minutes, except at 7 minutes. Group NE also had a higher heart rate (HR) than Group PE in most measurements. Both groups showed similar neonatal outcomes. CONCLUSION: Prophylactic infusion of 0.10 μg/kg/min norepinephrine was non-inferior to 0.60 μg/kg/min phenylephrine in terms of neonatal UA pH. These findings further support the safety of norepinephrine in obstetric anesthesia, although additional research is warranted to assess its long-term maternal and neonatal outcomes.